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Molecular analysis of p53 gene in laryngeal premalignant and malignant lesions. p53 protein immunohistochemical expression is positively related to proliferating cell nuclear antigen labelling index

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Abstract

This study was undertaken in order to investigate the molecular nature of the p53 gene in 19 laryngeal squamous cell carcinomas and dysplasias. Moreover, we have examined the possible relationship between proliferating cell nuclear antigen (PCNA) expression and p53 protein detection status in 42 laryngeal premalignant and malignant lesions in which 14 of the 19 samples used in the molecular study were included. p53 gene analysis was performed with the single-strand conformation polymorphism technique. PCNA was stained with the peroxidase/antiperoxidase immunohistochemical method using the monoclonal antibody PC-10. Data from previous work concerning p53 expression was used. We found that 9 of 12 of the immunohistochemically p53 positive (+) cases had mutations in exons 5 or 6. In the remaining immunohistochemically p53(+) and p53 negative (−) specimens there was no indication of sequence alterations. Furthermore, we did not observe any deletions in the chromosomal region 17p31.1 which encodes exons 4–8 of the p53 gene. The PCNA labelling index (LI) increased progressively with p53 protein detection status (percentage of cells immunohistochemically positive for p53). The difference between the group with the higher percentage of p53(+) cells and the others was statistically significant. These data show that although there is a discrepancy between immunohistochemical demonstration of p53 and molecular analysis, a large proportion of the former harbours the mutant form of the protein. In addition, p53 overexpression is positively correlated with PCNA LI, a finding which accompanies tumour progression.

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References

  1. Boyle JO, Hakim J, Koch W, Riet P van der, Hruban RH, Roa RA, Correo R, Eby YJ, Ruppert JM, Sidransky D (1993) The incidence of p53 mutations increases with progression of head and neck cancer. Cancer Res 53:4477–4480

    Google Scholar 

  2. Brachman DC, Graves D, Vokes E, Beckett M et al. (1992) Occurrence of p53 gene deletions and human papilloma virus infection in human head and neck cancer. Cancer Res 52:4832–4836

    Google Scholar 

  3. Chang CD, Ottavio L, Travalli S, Lipson KE, Baserga R (1990) Transcriptional and posttranscriptional regulation of the proliferating cell nuclear antigen gene. Mol Cell Biol 10:3289–3296

    Google Scholar 

  4. Chin KV, Ueda K, Pastan I, Gottesman MM (1992) Modulation of activity of the promoter of the human MDR1 gene by ras and p53. Science 255:459–462

    Google Scholar 

  5. Davis LG, Dibner MD, Battey JF (1986) Basic methods inmolecular biology. Elsevier, pp 315–317

  6. Deb S, Jackson CT, Subler MA, Martin DW (1992) Modulation of cellular and viral promoters by mutant human p53 proteins found in tumor cells. J Virol 66:6164–6170

    Google Scholar 

  7. Field JK, Zoumpourlis V, Spandidos DA, Jones AJ (1994) p53 expression and mutations in squamous cell carcinoma of the head and neck: expression correlates with patients' use of tobacco and alcohol. Cancer Detect Prev 18:197–208

    Google Scholar 

  8. Glinsberg D, Mechta F, Yaniv M, Oren M (1991) Wild type p53 can down-modulate the activity of various promoters. Proc Natl Acad Sci USA 88:9979–9983

    Google Scholar 

  9. Gorgoulis V, Giatromanolaki A, Karameris A, Tsatsanis C, Aninos D, Ozanne B, Velsemes M, Jordanoglou J, Trigidou R, Papastamatiou H, Spandidos DA (1993) Epidermal growth factor receptor expression in squamous cell lung carcinomas: an immunohistochemical and gene analysis in formalin-fixed, paraffin-embedded material. Virchows Arch [A] 423:295–302

    Google Scholar 

  10. Gorgoulis V, Rassidakis G, Karameris A, Barbatis C, Kittas C (1994) p53 expression in laryngeal squamous cell crcinomas and dysplasias. Possible correlation with HPV infection and clinicopathological findings. Virchows Arch 425:481–489

    Google Scholar 

  11. Gusterson BA, Anbazhgan R, Warren W et al. (1991) Expression of p53 in premalignant and malignant squamous epithelium. Oncogene 6:1785–1789

    Google Scholar 

  12. Hains SD, Landers EJ, Engle JL, George LD (1994) Physical and functional interaction between wild-type p53 and mdm-2 proteins. Mol Cell Biol 14:1171–1178

    Google Scholar 

  13. Hall AP, lane PD (1994) p53 in tumor pathology: Can we trust immunohistochemistry? Revisited! J Pathol 172:1–4

    Google Scholar 

  14. Harris AL (1990) Mutant p53 — The commonest genetic abnormality in human cancer? J Pathol 162:5–6

    Google Scholar 

  15. Jaskulski D, Gatti G, Travalli S, Calabretta B, Baserga R (1988) Regulation of the proliferating cell nuclear antigen cyclin and thymidine kinase mRNA levels by growth factors. J Biol Chem 263:10175–10179

    Google Scholar 

  16. Lechner MS, Mack DH, Finicle AB, Crook T, Vousden KH; Laimins LA (1992) Human papillomavirus E6 proteins bind p53 in vivo and abrogate p53-mediated repression of transcription. EMBO J 11(8):3045–3052

    Google Scholar 

  17. Levine AJ, Momand J, Finlay CA (1991) The p53 tumour suppressor gene. Nature 351:453–456

    Google Scholar 

  18. Maestro R, Dolcetti R, Gasparotto D, Doglioni C, Pelucchi S, Barzan L, Grandi E, Boiocchi M (1992) High frequency of p53 gene alterations associated with protein overexpression in human squamous cell carcinoma of the larynx. Oncogene 7:1159–1166

    Google Scholar 

  19. Mathews MB, Bernstein RM, Franza BR, Garrels JI (1984) Identity of the proliferating cell nuclear antigen and cyclin. Nature 303:374–376

    Google Scholar 

  20. Mercer WE, Shields MT, Lin D, Appela E, Ullrich SJ (1992) Growth suppression induced by wild — type p53 protein is accompanied by selective down — regulation of proliferating cell nuclear antigen expression. Proc Natl Acad Sci USa 88:1958–1962

    Google Scholar 

  21. Momand J, Zambetti GP, Olson DC, George D, Levine AJ (1992) The mdm-2 oncogene product forms a complex with p53 protein and inhibits p53 — mediated transactivation. Cell 69:1237–1245

    Google Scholar 

  22. Orita M, Iwahana H, Kanazawa H, Hayashi K, Sekiya T (1989) Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci USA 86:2766–2770

    CAS  PubMed  Google Scholar 

  23. Prives C (1994) How loops, β sheets, and a helices help us to understand p53. Cell 78:543–546

    Google Scholar 

  24. Reed M, Wang Y, Mayr G, Anderson ME, Schwedes JF, Tegtmeyer P (1993) p53 domains: suppression, transformation and transactivation. Gen Exp 3:95–107

    Google Scholar 

  25. Sommers KD, Merrick MA, Lopez ME, Incognito LS, Schechter GL, Casey G (1992) Frequent p53 mutations in head and neck cancer. Cancer Res 52:5997–6000

    Google Scholar 

  26. Subler MA, Martin DW, Deb S (1992) Inhibition of viral and cellular promoters by human wild-type p53. J Virol 66:4757–4762

    Google Scholar 

  27. Wynford-Thomas D (1992) p53 in tumour pathology: can we trust immunochemistry? J Path 166:329–330

    Google Scholar 

  28. Zambetti GP, Levine AJ (1993) A comparison of the biological activities of wild-type and mutant p53. FASEB J 7:855–865

    Google Scholar 

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Authors and Affiliations

  1. Laboratory of Histology and Embryology, University of Athens School of medicine, Athens, Greece

    V. Gorgoulis, G. Rassidakis & C. Kittas

  2. Department of Pathology, Red Cross Hospital, Athens, Greece

    V. Gorgoulis & C. Barbatis

  3. Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece

    V. Zoumpourlis & D. A. Spandidos

  4. Department of Pathology, 401 General Army Hospital, Athens, Greece

    A. Karameris

Authors
  1. V. Gorgoulis
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  2. G. Rassidakis
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  3. C. Kittas
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  4. C. Barbatis
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  5. V. Zoumpourlis
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  6. D. A. Spandidos
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  7. A. Karameris
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Gorgoulis, V., Rassidakis, G., Kittas, C. et al. Molecular analysis of p53 gene in laryngeal premalignant and malignant lesions. p53 protein immunohistochemical expression is positively related to proliferating cell nuclear antigen labelling index. Vichows Archiv A Pathol Anat 426, 339–344 (1995). https://doi.org/10.1007/BF00191341

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  • DOI: https://doi.org/10.1007/BF00191341

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